Effect of delaying surgery by more than 10 weeks after neoadjuvant therapy in rectal cancer: a single institution experience.

The optimal timing of surgery after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is still controversial. Aim of this study was to evaluate the effect of increasing time interval between the end of CRT and surgery on pathological outcomes. This is a retrospective analysis on 114 patients treated with long-course neoadjuvant RT with or without chemotherapy between January 2005 and September 2020. 43 patients underwent surgery within 10 weeks from the end of CRT (1st group), whereas 71 patients underwent total mesorectal excision with a time interval equal or greater than 10 weeks (2nd group). Primary endpoint was pCR (pathological complete response). Secondary endpoints were near pCR (ypT0-1 N0), tumor downstaging (ypT less than cT), nodal downstaging (ypN less than cN), and overall response comparing clinical with pathological TN stage. Overall, the pCR rate was 8.8%, whereas we observed no significantly difference in primary endpoint between the two groups. Considering near pCR, a trend toward significant difference in favor of 2nd group was seen (p = 0.072). Tumor and nodal downstaging rates were 39.5%, 41.9%, 59.2%, and 56.3% in the 1st and 2nd group, respectively, with a statistically significant difference for T category (p = 0.042). Overall response rates (TN stage) showed a trend toward significant difference in favor of patients of the ≥ 10 week group (p = 0.059). Our study suggests that a prolonged time interval between the end of CRT and surgery (≥ 10 weeks) increases pathological response rates.

Weekly pegylated liposomal doxorubicin and paclitaxel in patients with metastatic breast carcinoma: A phase II study.

Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m(2) PLD on Days 1, 8 and 15, plus 70 mg/m(2) paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3-4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity.

Docetaxel and gemcitabine in the treatment of metastatic breast carcinoma: a dose finding study.

AIMS AND BACKGROUND: Patients with metastatic breast cancer previously treated with anthracyclines for advanced disease are usually refractory to any further treatment with anthracyclines and have a poor prognosis. Therefore, new drugs or new combinations of drugs are needed. One approach has been to focus on the type of chemotherapy with low toxicity that preserves quality of life during treatment, such as weekly drug administration. STUDY DESIGN: We designed a dose-finding study to determine the maximum tolerated dose of gemcitabine plus docetaxel, given on a weekly schedule in metastatic breast cancer previously treated with anthracyclines. Three escalating doses of gemcitabine (900, 1000 and 1100 mg/m2) on days 1 and 8 in combination with a fixed dose of docetaxel, 35 mg/m2 on days 1 and 8 were planned. Dose-limiting toxicity included grade > 3 hematologic toxicity, grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if 1 out of 3 patients at any dose level experienced dose-limiting toxicity. RESULTS: Nine patients received a mean of 5.1 (range, 1-9) cycles. Gastrointestinal and leukopenia were the main dose-limiting toxicity. No patient experienced dose-limiting toxicity at dose level 1; at dose level 2, 2 out of 3 patients had dose-limiting toxicity and 3 additional patients treated at dose level 2 confirmed that the maximum tolerated dose had been reached. CONCLUSIONS: The recommended gemcitabine dose in combination with docetaxel (35 mg/m2 for a phase II study) was established at 900 mg/m2.

Weekly administration of gemcitabine plus docetaxel in patients with advanced breast cancer: a phase 1 study.

OBJECTIVE: This study was designed to determine the maximum tolerable dose (MTD) of gemcitabine plus docetaxel, both given on a weekly schedule, in patients with pretreated metastatic breast cancer (MBC). METHODS: Heavily pretreated patients with MBC, aged 18-75 years with World Health Organization performance status of 0-2 were enrolled. Three escalating weekly doses of docetaxel (30, 35 and 40 mg/m(2)) followed by a weekly fixed dose of gemcitabine, 800 mg/m(2), were administered on days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT) included grade > 3 hematologic toxicity and grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if > or = 3 of 5 patients at any dose level experienced DLT. RESULTS: Eighteen patients (median age 56 years) received a mean of 4.1 (range 1-6) cycles. Asthenia, stomatitis and leukopenia were the main DLTs. One of 5 patients had DLT at dose level 1 and 2 of 5 patients at dose level 2. At dose level 3, 3 of 5 patients had DLTs. Three additional patients treated at dose level 3 confirmed that the MTD had been reached. Therefore, the recommended docetaxel dose in combination with gemcitabine 800 mg/m(2) for phase II studies was established at the next lower dose, 35 mg/m(2). Of 12 evaluable patients, 7 (58%) achieved an objective response. CONCLUSIONS: Gemcitabine 800 mg/m(2) plus docetaxel 35 mg/m(2) on days 1, 8 and 15 of a 28-day cycle is a safe regimen which shows activity in heavily pretreated patients with MBC. Further phase II investigations with this combination are now warranted.